The goal of this project is to isolate, sequence, and characterize the genes expressed in human brain. As many as half of the almost 50,000 human genes are believed to be expressed in the brain. While sequencing half of the human genetic material is expected to take over a decade, and coding regions in the resultant genomic sequence may not be clearly discerned, sequencing a large number of cDNA clones can readily provide coding sequence data. We are building a large library of sequences of human brain cDNA clones. The availability of a broad-based library of cDNA sequences will facilitate identification of coding regions in genomic sequences as well as providing a starting point for individual cloning projects. A variety of approaches are being used to select brain-specific clones and to eliminate highly represented sequences. Over eight thousand human brain genes have been identified by this method. Computer analysis of DNA and predicted protein sequences were performed to search for the presence of conserved primary structure motifs and relationships to previously sequenced genes. It was found that over half of the sequences represented new genes with no detectable similarity to previously sequenced genes. An additional percentage represent the human homolog of genes that have been sequenced in other organisms. Further characterization of several interesting clones with potential roles in neural development is currently in progress and will include chromosome localization, examination of tissue distribution of expression, functional analysis, and evolutionary conservation.